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1 Department of Pediatrics, University of Colorado Health Sciences Center, Denver 80262; 2 Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, Colorado 80525; and 3 Exercise Science Research Institute, Arizona State University, Tempe, Arizona 85287
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Obesity results from
positive energy balance and, perhaps, abnormalities in lipid and
glycogen metabolism. The purpose of this study was to determine whether
differences in lipogenesis, retention of dietary fat, and/or
glycogenesis influenced susceptibility to dietary obesity. After 1 wk
of free access to a high-fat diet (HFD; 45% fat by energy) rats were
separated on the basis of 1 wk body weight gain into obesity-prone (OP;
48 g) or obesity-resistant groups (OR; 
40 g). Rats were either
studied at this time (OR1, OP1) or continued on the HFD for an
additional 4 wk (OR5, OP5). Weight gain and energy intake were greater
(P 0.05) in OP vs. OR at both 1 (53 ± 2 vs. 34 ± 1 g; 892 ± 27 vs. 755 ± 14 kcal) and 5 (208 ± 7 vs. 170 ± 7 g; 4,484 ± 82 vs. 4,008 ± 72 kcal) wk, respectively. Rats were
injected with 3H2O and were either provided
free access to an HFD meal containing labeled fatty acids (fed;
n = 10 or 11/group) or were fasted (n = 10/group) overnight. The amount of food or 14C tracer eaten
overnight was equivalent between OP and OR rats. In liver, the fraction
of 3H retained in glycogen or lipid was not significantly
different between OR and OP groups. Retention of dietary fat in the
liver was not increased in OP rats. In adipose tissue, retention of 3H was ~49% greater (P 0.05) in OP1 vs.
OR1 and ~30% greater in OP5 vs. OR5, but retention of dietary fat
was not elevated in OP vs. OR. At the same time, fat pad weight (sum of
epididymal, retroperitoneal, mesenteric) was 49% greater in OP1 rats
vs. OR1 rats and 65% greater in OP5 vs. OR5 rats (P 0.05). Thus a greater capacity for lipogenesis or retention of dietary
fat does not appear to be included in the OP phenotype. The
characteristic increase in energy intake associated with OP rats
appears to be necessary and critical to accelerated weight and fat gain.
tritium; liver; adipose tissue; energy intake; high-fat diet
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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OBESITY LARGELY RESULTS from an energy imbalance, where energy intake exceeds energy expenditure. The processes regulating both aspects of energy balance are complex. Although energy balance is an important determinant of obesity development, how nutrients are partitioned among tissues might also contribute to the development of obesity. For instance, in rats prone to the development of high-fat diet (HFD)-induced obesity, both lipoprotein lipase mRNA and activity were significantly greater in adipose tissue but were lower in skeletal muscle compared with rats resistant to obesity development (10). Likewise, the quantity of meal-derived fat retained in adipose tissue at both 2.2 and 6 h after meal consumption was significantly greater in obese Zucker rats (1). At the same time, the quantity of fat retained in skeletal muscle was significantly less in the obese Zucker rats relative to lean rats (1). Taken together, these data imply that inherent differences in the ability to partition meal-derived nutrients toward storage and away from oxidation contribute to obesity susceptibility and/or are a consequence of the obese state.
We have used an HFD model of obesity development to describe processes that differ between rats either prone or resistant to obesity development (OP and OR, respectively) early in their exposure to an HFD (35% carbohydrate, 45% fat). Several observations have been made regarding energy intake, nutrient partitioning, and weight gain using this model. When fed a low-fat diet (LFD; 68% carbohydrate, 12% fat), energy intake and weight gain are not significantly different between OP and OR rats (7, 10), but during the first 2 wk of HFD feeding, OP rats eat more and gain more weight than do OR rats. With longer term HFD feeding (5 wk), the differences between OP and OR rats in energy intake and weight gain are less pronounced. After 1 or 2 wk of HFD, OP rats exhibit a metabolic profile more conducive to carbohydrate use compared with OR rats in skeletal muscle, liver, and adipose tissue, but by 5 wk of HFD, these differences are no longer apparent (7, 10). Increased carbohydrate use may promote obesity development by reducing reliance on fat oxidation and/or partitioning carbohydrate into lipids via lipogenesis in liver or adipose tissue (6, 8, 16). Alternatively, a greater capacity for carbohydrate use may influence energy intake via effects on glycogen metabolism. For example, previous studies have suggested that whole body glycogen stores can influence energy intake (4, 5).
The present study was designed to determine whether glycogenesis, lipogenesis, and/or retention of dietary fat differed between OP and OR rats after overnight consumption of an HFD meal. Meal energy intake was held constant to determine whether obesity susceptibility was characterized by inherent differences in the capacity for nutrient partitioning among these metabolic pathways.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Experimental Animals, Diet and Feeding Protocol, and Group Classification
Male Wistar Crl(WI)BR rats (Sasco, Madison, WI), weighing between 135 and 180 g (7 wk of age) on arrival, were housed individually in a temperature-, humidity-, and light-controlled (12:12-h light-dark cycle) animal facility that met guidelines of the American Association for the Accreditation of Laboratory Animal Care. Throughout experiments, rats had free access to water. All protocols were approved by the University of Colorado Health Sciences Center Animal Care Committee.Rats were provided ad libitum access to a pelleted LFD (percent by
energy: 12% fat, 20% protein, 68% carbohydrate; Research Diets, New
Brunswick, NJ; Table 1) for a 2-wk
baseline period, followed by 1-wk ad libitum access to a pelleted HFD
(percent by energy: 45% fat, 20% protein, 35% carbohydrate; Research
Diets, Table 1). Rats were then separated on the basis of body weight gain during the 1st wk of HFD into either OP (body weight gain 48 g)
or OR (body weight gain 40 g) groups. These weight gain criteria were
selected a priori to ensure OP and OR rats were distinct with respect
to weight gain and that the weight gain criteria used to identify OP
and OR remained consistent across cohorts and were determined from
previous data from our laboratory (7, 10). A total of 81 animals was studied (5 cohorts). Rats with weight gains between 41 and
47 g were not studied further (31.1% of total rats fed the HFD).
Rats were studied either after 1 wk (OR1, OP1) or 5 wk of HFD feeding
(OR5, OP5) and were permitted ad libitum access to food until the night
before their day of study. In this model, 1 wk of HFD feeding
represents a time in which obesity is developing and is not yet
established; after 5 wk of HFD feeding, obesity is established. Thus
groups studied at 1 and 5 wk of HFD feeding permit comparisons of
processes associated with developing obesity and the established obese
state. Throughout the protocol, food intake was measured three times
per week (corrected for food spillage) and body weight was recorded
once per week.
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Study Procedures
On the morning before the day of study (between 1000 and 1100), body weight was determined and all food was removed. Water remained accessible. That evening (1700), one-half of the animals was provided an HFD meal (fed; HFD; percent energy: 45% fat, 20% protein, 35% carbohydrate), whereas the other one-half continued to fast (fasted). Immediately before the meal was provided, both fed and fasted rats were injected subcutaneously with 1.0 mCi 3H2O (1700). The following morning (0800), rats were anesthetized (subcutaneous administration of pentobarbital sodium, 50 mg/kg), body weight was determined, and animals were killed by exsanguination. Blood was collected into heparinized tubes from which plasma insulin, glucose, triglycerides, and the specific activity of plasma 3H2O were determined. The liver and fat pads (epididymal, retroperitoneal, and mesenteric) were removed within 2 min of death, weighed, and placed immediately into liquid nitrogen.Verification of steady state for plasma
3H2O over study day duration.
Separate studies (n = 4/weight class) were performed to
determine whether 3H2O in the plasma pool
remained in steady state for a period of time inclusive of the 15-h
study day protocol. Rats with body weights approximately equal to rats
maintained on HFD for 1 and 5 wk were permitted ad libitum access to a
standard chow diet. Four days before the day of study, a carotid artery
was catheterized as previously described (12). On the
morning of study (0900), 1.0 mCi of 3H2O was
injected subcutaneously. At 2, 4, 6, 8, and 24 h postinjection, arterial blood (100 µl) was collected for determination of plasma 3H2O. In these studies, the specific activity
of plasma 3H2O after subcutaneous injection of
1.0 mCi of 3H2O reached steady state some time
between 0 and 2 h and was maintained over 24 h (Fig.
1).
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14C-labeled HFD meal. The HFD meal was the same as the HFD rats had been consuming up to the day of study. To increase the likelihood that all food was consumed during the overnight study period and to equate energy intake/substrate delivery, the caloric value of the HFD meal (18.1 g, 95.4 kcal) was equal to 75% of the usual HFD intake of all rats during the 1st wk of HFD feeding. Because OP rats eat more during the 1st wk of HFD, OP rats were provided ~68% of their usual intake, and OR rats were provided ~82% of their usual intake. The HFD meal was labeled with equal proportions of 1-[14C]oleate, 1-[14C]palmitate, and 1-[14C]linoleate (total of 10 µCi of 14C added by way of 50 µl of olive oil to the HFD meal). These fatty acids represent the majority of fatty acids comprising the dietary fat in the HFD meal [corn oil: 11% palmitate, 25% oleate, and 55% linoleate (9)]. A combination of labeled fatty acids was used to trace the dietary fat provided in the HFD meal, because individual fatty acids are partitioned differently between oxidation and storage depending on chain length and degree of saturation (11). After tissue collection, individual cages in which the animals were housed between the time of 3H2O injection and death were swiped, and a portion of the shavings were counted to estimate losses of 3H and 14C through urine and the animals' handling of the labeled meal. Any remaining meal was collected, weighed, and counted for determination of the amount of meal and tracer not consumed during the overnight study period.
Analytic Methods
Blood analyses. Plasma glucose concentration was determined using a Beckman glucose analyzer (Glucose Analyzer II, Fullerton, CA). Plasma triglycerides were determined spectrophotometrically (Sigma Kit No. 320-A, Sigma Chemicals, St. Louis, MO). Insulin was determined by radioimmunoassay (Linco Research, St. Charles, MO).
Plasma 3H2O specific activity. Plasma was deproteinized overnight (14) with equal volumes of barium hydroxide and zinc sulfate (0.03 N). A portion of the resulting supernatant was counted, and the remainder was taken to dryness and counted. The difference in counts between the two portions represents 3H2O counts in plasma.
Tissue analyses. Liver glycogen was determined by the method of Chan and Exton (2). Liver triglyceride content and total lipid content of liver and adipose tissues were determined according to the methods of Denton and Randle (3).
Net lipogenesis, glycogenesis, and dietary fat retention. Aliquots of the extracts resulting from the determinations of liver glycogen and liver and adipose tissue lipid content were used to estimate net retention of both 3H and 14C dpm. Aliquots were taken to dryness, reconstituted with normal saline and 0.5 ml solvable (Sigma Chemicals), and counted (LS 6500, Beckman, Fullerton, CA).
Calculations
The specific activity of plasma 3H2O was calculated as follows: [3H dpm plasma (dpm/ml)]
[3H dpm remaining after drying (dpm/ml)] = 3H2O in plasma (dpm/ml). The density of
plasma (1.03 g/ml, a value intermediate to that of whole blood and
water) was used to convert 3H2O disintegrations
per minute per milliliter to disintegrations per minute per milligram.
Fraction of glycogen and lipid retained in liver and adipose tissue
over the 15-h study period was calculated as fractional 3H
retention = (3H dpm/mg of
tissue)/(3H2O dpm/mg in plasma). Data for the
fractional retention of 3H (Figs. 2B and
3B and Table 4) are presented as a percentage (fractional
retention × 100). An increase in the fractional retention of
3H as calculated above represents the contribution of net
glycogenosis or lipogenesis to the glycogen or lipid pool over the
period studied. Thus 100% retention would require that the specific
activity of glycogen be equal to the specific activity in plasma and
would suggest that the entire pool had been replaced over the period of
study. Data are also presented on a total tissue basis (Figs. 2D and 3D), where the fractional retention
(×100) was multiplied by organ weight. These data represent the
percentage of 3H retained in either glycogen or lipid by
the entire liver or fat pad.
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Percentage of dietary fat retained in liver and adipose tissue was calculated as (14C dpm within a total tissue/14C consumed in meal) × 100. Data are also expressed as a percentage of the 14C consumed in the meal within a gram of tissue (Table 5).
Data Analyses
Data related to glycogen concentration, tritium retention, and dietary fat retention are presented both relative to 1 g of tissue and to total tissue weight. A difference in tritium retention in glycogen when expressed per gram of tissue would be interpreted as an inherent difference in the capacity for glycogenesis and therefore would suggest that it may be causally linked to obesity susceptibility. In contrast, a difference in tritium retention in glycogen when expressed per total liver weight would be interpreted to be a consequence of the HFD, obesity, or both.Three-way ANOVA was used to determine the significance of group × time × fed/fasted interactions. Linear contrasts (determined a
priori) tested the significance of only certain comparisons of interest
between OP and OR groups (e.g., difference between fed and fasted OP1
rats vs. OR1 rats). When one-way ANOVA in combination with necessary
multiple-comparison tests (15) was used to detect differences across groups, interpretations were the same as those made
using linear contrasts. Because the results from the one-way ANOVA and
subsequent multiple comparisons offer more information to the reader,
data are reported using these statistics. Significance was set at
P 0.05 for all comparisons. For fractional retention of
3H expressed relative to the epididymal and retroperitoneal
fat pads, an outlier (greater than 2 standard deviations from the mean)
in both the OR1 fed group and the OR1 fasted group, respectively, was
excluded from the statistical analysis. These two analyses then have
one less observation than all other analyses.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Body Weight, Energy Intake, and Body Weight Gain
Initial body weight was not significantly different among groups (Table 2). During the second week of LFD, energy intake among 1 and 5 wk rats was not significantly different. Body weight gain during the baseline period was significantly greater in OP1 fed rats compared with OR1 fed rats.
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As anticipated from the study design, after the 1st wk of HFD, OP1 rats
ate more (18%; P 0.05) and gained more weight (55%; P 0.05) than did OR1 rats. Over the 5-wk HFD feeding
period, energy intake was 12% greater (P 0.05) and
weight gain was 22% greater (P 0.05) in OP5 vs. OR5.
HFD Meal Intake
OP and OR rats were provided the same number of calories for the overnight HFD meal, and the number of kilocalories consumed was not different among rats (P > 0.05; OP1, 89.3 ± 4.0 kcal; OR1, 93.0 ± 2.9 kcal; OP5, 82.9 ± 4.2 kcal; OR5, 87.3 ± 4.0 kcal). The HFD meal provided ~70, 86, 66, and 78%, respectively, for OP1, OR1, OP5, and OR5 of their usual intake during their 1st wk of HFD feeding.Tissue Weights
Liver weight was greater in OP1 vs. OR1 in the fed state (Table 3, P 0.05). Liver weight
was greater in OP5 vs. OR5 in the fasted state (P 0.05).
Liver weight was greater (P 0.05) in fed compared
with fasted rats at both 1 and 5 wk. Fat pad weights (epididymal, retroperitoneal, and mesenteric) were 49% greater in OP1
vs. OR1 (P > 0.05) and 65% greater in OP5 vs. OR5
(P 0.05; Table 3).
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Plasma Substrates and Hormones
Plasma glucose, insulin, and triglyceride concentrations were not significantly different between fed OP and OR rats or between fasted OP and OR rats (Table 3). Glucose and triglyceride concentrations were greater (P 0.05) in the fed vs. fasted state for all groups.
Glycogen Concentrations and Fractional 3H Retention in Glycogen
Fed liver glycogen concentration (per gram liver) was lower (P 0.05) in OP5 compared with OR5, OR1, and OP1 rats
(Fig. 2A). Total liver
glycogen content (glycogen per total liver weight) in the fed state was
greater (P 0.05) in fed OR5 compared with all other
groups (Fig. 2C). 3H retention in glycogen per
gram of liver was greater (P 0.05) in OR1 compared with
all other fed groups (Fig. 2B). Total 3H
retention in glycogen was not significantly different among groups
(Fig. 2D).
Liver Triglyceride Concentrations and Fractional 3H Retention in Lipid
Liver triglyceride concentrations were greater (P 0.05) in OP5 vs. OR5 in the fasted state only (Fig.
3A). Total liver triglyceride content was higher (P 0.05) in fasted OP5 vs. OR5 rats
and in fed OP5 vs. OR5 rats (Fig. 3C). 3H
retention in liver lipid was not significantly different among 1 wk
rats (Fig. 3, B and D). At 5 wk, 3H
retention was also not significantly different when OP and OR rats were
compared in the fasted or fed state (Fig. 3, B and
D).
Adipose Tissue Fractional 3H Retention in Lipid
In the fasted state, 3H fractional retention was not significantly different between OP1 and OR1 or between OP5 and OR5 whether expressed per gram or per total fat pad weight (Table 4). In the fed state, 3H fractional retention was not significantly increased in OP rats when expressed per gram of tissue weight (Table 4). In fact, 3H fractional retention was lower (P 0.05) in the
mesenteric fat pad in OP1 rats vs. OR1 (Table 4). 3H
fractional retention relative to total fat pad mass in OP1 vs. OR1 rats
was increased by 30% (P > 0.05) and 49%
(P 0.05) under fasted and fed conditions, respectively,
and was increased (P > 0.05) by 55 and 30% in OP5 vs.
OR5 under fasted and fed conditions, respectively.
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Percentage of 14C From HFD Meal Retained in Liver and Adipose Tissue
The amount of 14C tracer consumed was not significantly different among fed animals (Table 5). In both liver and adipose tissue, the percent of 14C retained (per gram or total tissue weight) was lower in OP1 vs. OR1 (P 0.05), but was not
significantly different between OP5 and OR5 rats (Table 5).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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General Findings
In the present study, the overnight postprandial response to an HFD meal was determined in OP and OR rats. To evaluate whether susceptibility to dietary obesity involved differences in the capacity to partition dietary nutrients into storage pathways, energy intake was equated. Under these conditions, estimated net lipogenesis and retention of dietary fat per gram of adipose tissue or liver were not increased in OP rats. However, when expressed relative to total fat pad mass, adipose tissue lipogenesis was increased in OP rats. These data imply that OP rats are not characterized by an increased capacity for lipogenesis or retention of dietary fat. Net liver glycogenesis and the ability to restore the liver glycogen pool to fed levels were not significantly different between OP and OR groups after 1 wk on the HFD. However, the ability to restore the liver glycogen pool was significantly reduced in OP rats after 5 wk on the HFD. These results suggest that changes in liver glycogen metabolism may be the result of the greater adiposity and/or energy intake in OP rats.Hepatic and Adipose Tissue De Novo Lipogenesis and Retention of Dietary Fat
Although liver triglyceride concentration was elevated in OP rats after 5 but not 1 wk of HFD feeding, retention of tritium in the hepatic lipid pool (estimate of net lipogenesis) was not significantly different between OP and OR rats at either 1 or 5 wk. In adipose tissue, although the summed fat pad weight in OP1 rats was not higher statistically, it weighed 49% more than in OR1 rats (Table 3; average of fed and fasted). By 5 wk, the summed fat pad weight was 65% greater (P 0.05) in OP5 rats vs. OR5 rats (Table 3). However,
retention of tritium in adipose tissue (estimate of net lipogenesis)
when expressed per gram of tissue was not increased in OP rats at
either 1 or 5 wk. Thus OP rats are not characterized by an increased
capacity for net lipogenesis in liver or adipose tissue in response to
a single HFD meal. The fact that estimated net lipogenesis was
significantly greater in OP rats only if expressed relative to total
fat pad mass provides further support for the notion that differences in the capacity of partitioning nutrients toward storage via
lipogenesis do not contribute to susceptibility to dietary obesity.
Similar to lipogenesis, there was no evidence for increased retention of dietary fat in liver and adipose tissue of OP rats. If anything, OP rats retained less dietary fat in these tissues. We previously reported that adipose tissue lipoprotein lipase mRNA and activity was elevated in OP rats after 1 and 2 wk of HFD feeding (10). Taken together, these data suggest that the increased lipoprotein lipase does not impart a greater capacity to retain dietary lipid in adipose tissue in response to a single meal.
The percentage of tritium and labeled dietary lipids retained in liver and adipose tissue lipids was not significantly increased between 1 and 5 wk, despite the fact that both liver and adipose tissue weights were increased. Thus either meal-stimulated synthesis/storage was reduced or lipid mobilization was increased between 1 and 5 wk of HFD feeding in both groups. The extent to which this observation involves changes in insulin action requires further study.
The meal feeding period in the present study encompassed 15 h. Over the 15-h period, animals from both dietary groups ate a similar amount of energy and, thus, a similar nutrient mixture. This procedure was chosen so that net nutrient storage could be assessed under usual feeding conditions (i.e., free access to the diet throughout the night) but without differences in energy intake. However, free access to the diet throughout the night did not allow us to control or equate the timing of food intake between groups. Thus it is possible that food consumption occurred over different time courses between dietary groups. The impact of this is difficult to determine but should be considered when comparing these results with other studies. We chose to make measurements at only one time point after the end of the HFD meal feeding period. Data reported by others have indicated that by 2.2 h postmeal, obese Zucker rats retained significantly more dietary fat in liver and adipose tissue than lean rats; by 6 h postmeal, the differences between obese and lean rats were even more striking (1). Thus it is likely that the choice of a single 15-h time point was not the reason for the lack of differences between OP and OR rats. In addition, comparison of the results from the present study with those of the study involving Zucker rats suggests that the contribution of nutrient partitioning may be greater in genetic vs. dietary obesity.
Liver Glycogen and Net Glycogenesis
The only observed difference between OP and OR rats after 1 wk on the HFD was in the retention of tritium when expressed per gram of liver. Less retention of tritium suggests that net glycogenesis was reduced in OP vs. OR rats. Because liver glycogen concentration was not significantly different, these data imply that glycogen turnover was reduced in OP rats. The impact of a reduced glycogen turnover to obesity development in this model is difficult to assess; however, because it was observed early in the course of HFD feeding, it may represent an inherent difference between OP and OR rats.By 5 wk of HFD feeding, retention of tritium in glycogen was not different between OP and OR rats, but liver glycogen concentration (expressed per gram or per total liver) was significantly lower in OP rats, suggesting that OP rats mobilize more glycogen over the course of the 15-h meal feeding period. It is likely that this impairment results from the greater adiposity and, perhaps, greater insulin resistance at the liver in OP rats.
Importance of Energy Intake to the OP Phenotype
In the present study, energy intake was equated between OP and OR rats to evaluate the inherent capacities for postprandial lipogenesis, retention of dietary lipid, and glycogenesis. Under these conditions, OP rats do not display a greater capacity for accumulation of lipid via lipogenesis or retention of dietary lipid. These data, therefore, underscore the significance of the increased energy intake to the OP phenotype. In fact, these data suggest that the presence of a positive energy balance, brought about by increased energy intake, represents the critical stimulus to increased body weight gain in OP rats.Perspectives
The data presented here indicate that with equicaloric feeding, OP rats neither store more dietary fat nor undergo greater rates of lipogenesis than do OR rats, and, therefore, underscore the central role of energy intake in diet-induced obesity. At present, it is unclear what mechanism(s) drive the greater intake by OP rats during their early exposure to an HFD. Concentrations of certain metabolites and hormones such as
-hydroxybutyrate, corticosterone, insulin, or
leptin, each of which can impact food intake, do not seem to account
for the increased intake by OP rats with HFD feeding. However,
differences in sensitivity to any of these substrates or hormones (or
others not yet investigated) may exist between OP and OR rats.
Importantly, differences in energy intake between OP and OR rats are
only manifest when dietary fat content is high. As such, it can be
hypothesized that OP rats increase energy intake in response to an HFD
in an attempt to acquire adequate carbohydrate.
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ACKNOWLEDGEMENTS |
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We gratefully acknowledge the metabolic core of the Colorado Clinical Nutrition Research Unit (P30-DK-48520-01) for assistance with insulin measurements. We also thank Dr. Gary Grunwald (University of Colorado Health Sciences Center) for assistance with the statistical analyses of these data.
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FOOTNOTES |
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This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-55386 (to M. J. Pagliassotti) and DK-38088 (to J. O. Hill), and the Colorado Agricultural Experiment Station Project 616 (to C. L. Melby).
Address for reprint requests and other correspondence: S. R. Commerford, Dept. of Medicine/Endocrinology, Univ. of Pittsburgh Medical Center, E1112 Biomedical Science Tower, Lothrop St., Pittsburgh, PA 15261 (E-mail: commerfordr{at}msx.dept-med.pitt.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 18 October 2000; accepted in final form 16 January 2001.
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REFERENCES |
|---|
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Bessesen, DH,
Rupp CL,
and
Eckel RH.
Dietary fat is shunted away from oxidation, toward storage in obese Zucker rats.
Obesity Res
3:
179-189,
1994[ISI][Medline].
2.
Chan, TM,
and
Exton JH.
A rapid method for the determination of glycogen content and radioactivity in small quantities of tissue or isolated hepatocytes.
Anal Biochem
71:
96-105,
1976[ISI][Medline].
3.
Denton, RM,
and
Randle PJ.
Concentrations of glycerides and phospholipids in rat heart and gastrocnemius muscles: effects of alloxan-diabetes and perfusion.
Biochem J
104:
416-422,
1967[ISI][Medline].
4.
Flatt, JP.
Dietary fat, carbohydrate balance and weight maintenance; effects of exercise.
Am J Clin Nutr
45:
296-306,
1987
5.
Flatt, JP.
Glycogen levels and obesity.
Int J Obes
20:
S1-S11,
1996.
6.
Froidevaux, F,
Schutz Y,
Christin L,
and
Jequier E.
Energy expenditure in obese women before and during weight loss, after refeeding, and in the weight-relapse period.
Am J Clin Nutr
57:
35-42,
1993
7.
Gayles, EC,
Pagliassotti MJ,
Prach PA,
Koppenhafer TA,
and
Hill JO.
Contribution of energy intake and tissue enzymatic profile to body weight gain in high-fat fed rats.
Am J Physiol Regulatory Integrative Comp Physiol
272:
R188-R194,
1997
8.
Larson, DE,
Ferraro RT,
Robertson DS,
and
Ravussin E.
Energy metabolism in weight-stable postobese individuals.
Am J Clin Nutr
62:
735-739,
1995
9.
Linscheer, W,
and
Vergroesen A.
Lipids.
In: Modern Nutrition in Health and Disease. Philadelphia, PA: Lea & Febiger, 1994, p. 47-88.
10.
Pagliassotti, MJ,
Knobel SM,
Shahrokhi KA,
Manzo AM,
and
Hill JO.
Time course of adaptation to a high-fat diet in obesity-resistant and obesity-prone rats.
Am J Physiol Regulatory Integrative Comp Physiol
267:
R659-R664,
1994
11.
Pai, T,
and
Yeh Y.
Stearic acid, unlike shorter-chain saturated fatty acids, is poorly utilized for triacylglycerol synthesis and beta-oxidation in cultured rat hepatocytes.
Lipids
31:
159-164,
1996[ISI][Medline].
12.
Popovic, V,
and
Popovic P.
Permanent cannulation of aorta and vena cava in rats and ground squirrels.
J Appl Physiol
15:
727-728,
1960
13.
Reeves, PG,
Nielsen FH,
and
Fahey J.
AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition Ad Hoc Committee on the Reformulation of the AIN-76A Rodent Diet.
J Nutr
123:
1939-1951,
1993.
14.
Somogyi, M.
Determination of blood sugar.
J Biol Chem
160:
69-73,
1945
15.
Tukey, JW.
A quick compact two-sample test to Duckworth's specifications.
Technometrics
1:
31-48,
1959.
16.
Zurlo, F,
Lillioja S,
Esposito-Del Puente A,
Nyomba BL,
Raz I,
Saad MF,
Swinburn B,
Knowler WC,
Bogardus C,
and
Ravussin E.
Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24h RQ.
Am J Physiol Endocrinol Metab
259:
E650-E657,
1990
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  M. R. Jackman, A. Steig, J. A. Higgins, G. C. Johnson, B. K. Fleming-Elder, D. H. Bessesen, and P. S. MacLean Weight regain after sustained weight reduction is accompanied by suppressed oxidation of dietary fat and adipocyte hyperplasia Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2008; 294(4): R1117 - R1129. [Abstract] [Full Text] [PDF]
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 M. T. Timlin, B. R. Barrows, and E. J. Parks Increased Dietary Substrate Delivery Alters Hepatic Fatty Acid Recycling in Healthy Men Diabetes, September 1, 2005; 54(9): 2694 - 2701. [Abstract] [Full Text] [PDF]
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K. E. Wortley, G.-Q. Chang, Z. Davydova, and S. F. Leibowitz Peptides that Regulate Food Intake: Orexin gene expression is increased during states of hypertriglyceridemia Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2003; 284(6): R1454 - R1465. [Abstract] [Full Text] [PDF]
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W. A. Cupples Regulating food intake Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2003; 284(3): R652 - R654. [Full Text] [PDF]
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W. A. Cupples Regulation of body weight Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2002; 282(5): R1264 - R1266. [Full Text] [PDF]
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